Multi-omics analysis revealed the mitochondrial-targeted drug combination to suppress the development of lung cancer

Abstract

The incidence and mortality of lung cancer have continued to rise in recent years. Mitochondrial energy metabolism malfunction is crucial for cancer cell death, proliferation and bioenergetic reprogramming.Improving the mitochondrial activity is a potent method to arrest tumor development and growth. In this study, we attempted to use mitochondrial targeting drugs to improve mitochondrial function and reverse the Warburg effect in the treatment of lung cancer MethodsIn this study, we created a mouse subcutaneous tumor model, treated it with multiple mitochondrialtargeted drug combinations, and analyzed the tumor tissues by transcriptomic, proteomic and metabolomic methods. ResultsUse of target drugs to improve the level of mitochondrial energy metabolism can effectively prevented cancer occurrence and progression, especially the 7-drug combination regimen, which producing healthy mitochondria from the three aspects of mitochondrial membrane, electron chain and interaction substrate. The NK cells in tumor tissue were increased effectively and the tumor markers in plasma were decreased. And we mapped the protein interaction network using omics data found the 7-drug combination therapy lung cancer by up-regulating mitochondrial oxidative phosphorylation-related genes, down-regulating proliferation-and validation-related genes and reversing tumor metabolic remodeling. ConclusionsMitochondrial targeted drug cocktail therapy can effectively inhibit the occurrence and development of tumors, which is due to the reprogramming of energy metabolism in tumor tissues and the increase of immune cells. Our study offers a novel approach for the clinical prevention and treatment of lung cancer, and provides evidence-based clues for the combined use of targeted mitochondrial drugs.